Document Detail

Hyperkalemia alters endothelium-dependent relaxation through non-nitric oxide and noncyclooxygenase pathway: a mechanism for coronary dysfunction due to cardioplegia.
MedLine Citation:
PMID:  8633948     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Reported results of hyperkalemia (cardioplegia or organ preservation solutions) on endothelial function are contradictory. The endothelium-dependent relaxation is related to three major mechanisms: cyclooxygenase, nitric oxide, and endothelium-derived hyperpolarizing factor (K+ channel related). The present study was designed to test the hypothesis that hyperkalemia may alter endothelial function through non-nitric oxide and noncyclooxygenase pathways. METHODS: Porcine coronary artery rings (5 to 10 in each group) were studied in organ chambers under physiologic pressure. After incubation with 20 or 50 mmol/L K+ for 1 hour, the response to substance P, an endothelium-dependent vasorelaxant peptide, in K+ (25 mmol/L)-induced contraction was studied in the presence of the cyclooxygenase inhibitor indomethacin (7 mumol/L), the nitric oxide biosynthesis inhibitor NG-nitro-L-arginine (L-NNA) (300 mumol/L), or the adenosine triphosphate-sensitive K(+)-channel blocker glybenclamide (3 mumol/L) in comparison with control arteries (69.8 +/- 4.6% of K+ contraction). RESULTS: Without exposure to hyperkalemia, indomethacin (with or without glybenclamide) did not alter but L-NNA significantly reduced the relaxation (39.7% +/- 3.7%, p < 0.001). After exposure to K+, the indomethacin- and L-NNA-resistant relaxation was further reduced (7.4% +/- 3.2% for 20 mmol/L K+, p < 0.0001; or 13.5% +/- 8.4% for 50 mmol/L K+, p < 0.05, compared with rings without exposure), whereas the indomethacin- and glybenclamide-resistant relaxation was not altered. Incubation with hyperkalemia (50 mmol/L) also significantly reduced the sensitivity (increased EC50) of the indomethacin- and L-NNA-resistant relaxation (-9.75 +/- 0.06 versus -9.33 +/- 0.04 log M, p < 0.01). CONCLUSIONS: Exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant, endothelium-dependent (endothelium-derived hyperpolarizing factor-related) relaxation. Our study may suggest a new mechanism of coronary dysfunction after exposure to hyperkalemia and open a new area for protection of coronary endothelium in cardiac surgery and for organ preservation in transplantation surgery.
G W He; C Q Yang
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  61     ISSN:  0003-4975     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  1996 May 
Date Detail:
Created Date:  1996-07-02     Completed Date:  1996-07-02     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1394-9     Citation Subset:  AIM; IM    
Department of Surgery, University of Hong Kong, Grantham Hospital, Aberdeen, Hong Kong.
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MeSH Terms
Cardioplegic Solutions / pharmacology*
Coronary Vessels / drug effects*,  physiology
Cyclooxygenase Inhibitors / pharmacology
Endothelium, Vascular / drug effects*,  metabolism,  physiology
Heart Arrest, Induced / adverse effects
Heart Diseases / etiology,  physiopathology
Indomethacin / pharmacology
Nitric Oxide / pharmacology,  physiology*
Reg. No./Substance:
0/Cardioplegic Solutions; 0/Cyclooxygenase Inhibitors; 10102-43-9/Nitric Oxide; 53-86-1/Indomethacin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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